Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature (ThrasherAI)

This study has been completed.

Sponsor:

Nemours Children's Clinic

ClinicalTrials.gov Identifier:

NCT01248416

First Posted: November 25, 2010

Last Update Posted: September 23, 2016

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

When treating very short children in puberty we are time-limited, as sex hormones cause the growth plates to fuse and growth to end. Growth Hormone (GH), plus drugs that stop puberty, increase height potential, but leave children sexually infantile at a critical time in development. Human and animal data show that estrogen, in females and males, is a principal regulator of the fusion of the growth plate in puberty. Using aromatase inhibitors (AIs), which block testosterone to estrogen conversion, in boys with different growth disorders, we have shown that AIs may have beneficial effects enhancing height potential in growth-retarded males, without affecting their puberty. However, no direct comparison of the effect of AIs alone vs. conventional GH treatment has been done to date. This study will assess the effect of AIs alone, GH alone and combination treatment in enhancing height potential in adolescent boys with idiopathic short stature.

To assess the safety and efficacy of AIs alone, vs. GH alone, vs. AIs and GH increasing adult height potential in adolescent boys with idiopathic short stature treated for 2 years. [ Time Frame: 3 to 4 years ]

Adolescent boys with idiopathic short stature will be randomized to either AI orally (anastrozole or letrozole), GH subcutaneously or AI with GH combination for 2 years and 1 extra year post treatment follow up . Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy. Blood samples and bone age X rays will be obtained during routine clinic visits. Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years). Differences in height gains (cm) will be compared among the 3 groups as well. Number of participants with adverse events as a measure of safety and tolerability will be recorded.

Secondary Outcome Measures:

To characterize bone density and bone turnover markers as well as bone morphology in all 3 groups. [ Time Frame: 3 to 4 years ]

This secondary end point includes the changes in bone density (gm/cm2), IGF-I concentrations, and bone markers concentrations. A Dexa scan with a lateral view of the thoracic spine as well as blood work will be routinely done at baseline, 1 year and 2 years and changes in the 3 groups compared over time. Subjects who have completed 2 years of therapy, may receive a 3 year scan if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.

To investigate if the combination of GH with an AI has additive effects increasing lean body mass in puberty as compared to each compound alone. [ Time Frame: 3 to 4 years ]

This secondary outcome measures lean body mass (kg) by Dexa scan and body mass index measurements at baseline, 1 and 2 years. A comparison of the changes among the 3 groups over time will be done. Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.

To assess the degree of suppression of aromatase using letrozole vs anastrozole using highly sensitive LCMSMS assays. [ Time Frame: 3 to 4 years ]

Data on the subjects using either AI will be used for the overall efficacy analysis. The degree of suppression of estradiol by each AI will be indirectly assessed by using a sensitive estradiol assay. This secondary outcome measures serum testosterone, estrone and plasma estradiol concentrations. Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.

Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years

Drug: Growth Hormone

Other Names:

Nutropin (Somatropin)

Genotropin (Somatropin)

Active Comparator: Aromatase Inhibitor and Growth Hormone

Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years

Drug: Aromatase Inhibitor

Other Names:

Arimidex (Anastrozole)

Femara (Letrozole)

Drug: Growth Hormone

Other Names:

Nutropin (Somatropin)

Genotropin (Somatropin)

Drug: Aromatase Inhibitor and Growth Hormone

Other Names:

Arimidex (Anastrozole)

Femara (Letrozole)

Nutropin (Somatropin)

Genotropin (Somatropin)

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:

12 Years to 18 Years (Child, Adult)

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Males: Ages: 12 - less than 18 years.

Bone age less than 14 ½ years at study initiation.

Presence of puberty.

Idiopathic short stature will be defined as a short child equal or less than -2SD for height, with normal GH responses to stimuli (> or = 5ng/ml to at least 2 secretagogues) or a normal IGF-I and BP-3, normal body proportions and no other identifiable growth pathology.

Accurate growth data for at least 6 months at baseline is available.

Exclusion Criteria:

Chronic illnesses.

Chronic use of glucocorticosteroids.

Previous use of hormonal treatment with AIs, sex steroids or GH in the preceding 6 months.

Birth weight small for gestational age (SGA).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01248416